Table 4.
Neuromuscular and pain signalling effects of Muricidae extracts and compounds; (a) Choline ester and hypobranchial gland (HG) muscle relaxing and nicotinic activity; (b) Isatin derivative neurotransmitters, analgesics and sedative properties of the Muricidae extracts and compounds.
| (a) | ||||||
| Source Compound a | Conc. | Assay/in Vivo Model | Observed Effects | |||
| HG Extract/Synthetic | Neuromuscular block Paralysis of the skeletal musculature after intravenous (i.v.) administration. Murexine stimulates nicotinic acetylcholine receptors opening the monovalent cation channel for depolarization of the motor endplate. Mild or no muscarine like activity was detected in guinea-pig and rabbit intestine, rabbit atrium and isolated frog heart assays. | |||||
| M, MCH, DHM, SCH | various | Frog rectus abdominis muscle assay [74,76,140] | ||||
| M, MCH | 0.75 mg/assay | Neuromuscular block in rat diaphragm assay [140] | ||||
| M, MCH | 100–2000 μg/kg | % Twitch reduction assays on cat, dog and rabbit gastro-cnemius were used to calculate concentration effect [75] | ||||
| M, MCH | 0.65 mg/kg | 50% rabbit head drop after i.v. injection [74] | ||||
| DHM | 0.52 mg/kg | |||||
| M, MCH | 0.35 mg/kg | 50% dog paralyzing dose after i.v. injection [140] | ||||
| DHM | 0.022 mg/kg | |||||
| M, MCH | 1.0–1.2 mg/kg | Relaxing effect in human preliminary clinical trial on 160 patients after a single i.v. injection [140] | ||||
| HG Extract/Synthetic | Nicotinic activity Murexine i.v. at high dose is likely to have nicotinic effects on sympathetic ganglia and adrenal medulla | |||||
| M | 60 μg/kg/min (no effect) | Nicotinic effects of murexine showed a dose dependant rise in blood pressure whilst inducing neuromuscular block in anaesthetised cats and dogs [74,140,141] | ||||
| M | 300 μ/kg | |||||
| (b) | ||||||
| Compound | Conc. | Assay/in Vivo Model and Effects Observed | Method Admin. | Mode of Action/Pathways Identified | Overall Effects | |
| 2,3 dioxoindoline | 15–20 mg/kg | Mice and rats showed anxiogenic behaviour in the open-field and elevated plus maze test and the social interaction test [142] | i.p. | Monoamine oxidase B inhibition as a contribution to stress related tribulin activity. | Anxiogenic at low dose | |
| <50 mg/kg | Mice showed immobility in the forced swim test [143] | i.p. | Inhibits monoamine oxidase affecting monoamine levels. | Sedative at high dose | ||
| indole-2,3-dione | 20 mg/kg | Isatin administered after pentylenetetrazole (PTZ) and 3-mercaptopropionic acid (3MPA) induced seizures in rats [143] | i.p. | Antagonise natriuretic peptide receptor A (NPR-A) and NPR-C signalling at low dose due to the metabolite 5-hydroxyisatin. | Proconvulsant at low dose | |
| 60–80 mg/kg | Effective against PTZ and 3MPA induced clonic convulsions [144] | i.p. | Anticonvulsant at high dose | |||
| indole-2,3-dione-3-oxime or as salt, oxide or hydrate derivative | 10 uM | Intermediate-conductance and small-conductance Ca(2+)-activated potassium channel (IKCa and SKCa)activation in a 15 ul cell chamber on human embryonic kidney 293 cell line [145] | immersion | Ikca and SKca ion channel associated conditions including respiratory conditions, muscle spasms, convulsive conditions, mood disorders and dementia. | Ikca and Skca ion channel activation | |
| 5,7-dinitro-1-methyl-1H-indole-2,3-dione-3-(0-methyloxime) | 0.1–10 mg/kg | Administered to NMRI mice for ATPA rigidity, to DAB/2 mice for quisqualate seizures, to NMRI mice for N-methyl-d-aspartate (NMDA) seizures and to NMRI mice for cocaine hypermotility [146] | i.v. and orally (cocaine hypermotility) | Excitatory amino acid antagonist blocking glycine and glutamate on the quisqualate, 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propionic acid (ATPA), 2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainate and NMDA receptors. | Anticonvulsant for ATPA quisqualate, NMDA seizures and cocaine hypermotility | |
| 5-bromoisatin | 200 mg/kg | Phenylquinone test for analgesia in mice showing 90% inhibition after 30 min [147] | i.p. | 5-bromoisatin was comparable to acetylsalicylic and showed analgesia with fewer side effects. | Analgesic | |
| 400 mg/kg | Randall and Selitto test for analgesic comparison in rats [147] | orally | ||||
| 90 mg/kg | Overall ED50 after 30 min reaction time [147] | |||||
a M—murexine, was extracted from Murex trunculus, Murex brandaris and Tritonalia erinacea; MCH—murexine chloride hydrochloride (synthetic); DHM—dihydromurexine; and SCH—senecioylcholine are from hypobranchial gland extracts of the above species. Administration method includes: i.p.—intraperitoneal and i.v.—intravenous.